Studies into the preparation of 1-deoxy-1-thiocyanato-d-glycopyranosyl cyanides and the anomeric effect of the thiocyanate group

The reaction of per-O-acetylated 1-bromo-1-deoxy-α-d-arabinopyranosyl cyanide with thiocyanate ions gave the corresponding 1-deoxy-1-thiocyanato-α- and β-d-arabinopyranosyl cyanides. In the reaction of the per-O-acetylated 1-bromo-1-deoxy-β-d-xylopyranosyl cyanide and its per-O-benzoylated β-d-glucopyranosyl analogue the corresponding 2-hydroxy-glycal esters formed in addition to the anomeric pair of thiocyanato-cyanides. The formation of 2,3,4,6-tetra-O-benzoyl-α-d-glucopyranosyl thiocyanate was demonstrated in the reaction of benzobromoglucose with thiocyanate ions. The equilibrium constant between 2,3,4,6-tetra-O-acetyl-1-deoxy-1-thiocyanato-α- and β-d-galactopyranosyl cyanides was determined. Based on this value, the equilibrium ratio for the 2,3,4,6-tetra-O-acetyl-α- and β-d-galactopyranosyl thiocyanates was calculated to be 94:6, and the anomeric effect of the SCN group was estimated to exceed 3 kcal/mol. X-Ray crystallographic data support endo- and exo-anomeric effects of the SCN moiety.     

β-Mannosylation of N-acetyl glucosamine by propargyl mediated intramolecular aglycon delivery (IAD): synthesis of the N-glycan core pentasaccharide

An efficient and completely stereocontrolled synthesis of the N-glycan Manβ(1-4)GlcNAc disaccharide is achieved by propargyl mediated intramolecular aglycon delivery (IAD). Isomerisation of the 2-O-progargyl group of a manno thioglycoside to an allene is followed by iodonium ion mediated mixed acetal formation with the 4-OH of a protected GlcNAc derivative, and subsequent intramolecular glycosylation with complete control of anomeric stereochemistry. Access to this key disaccharide intermediate allows completion of the total synthesis of the core N-glycan pentasaccharide.     

Hafinium (IV) promoted synthesis of 2,3-unsaturated N- and C-pseudoglycosides via Type I Ferrier Rearrangement

By using Hf(OTf)₄ as the catalyst, a series of 2,3-N- and C-unsaturated-glucosides have been synthesized from 3,4,6-tri-O-acetyl-d-glucal, 2,4,6-tri-O-benzyl-d-glucal and ((2R,3S)-3-acetoxy-2,3-dihydrofuran-2-yl)methyl acetate under mild reaction conditions in good yields with high anomeric selectivities.     

HSAB-driven regioselectivity difference in the Lewis-acid catalyzed reactions of 2-C-substituted glycals with sulfur and oxygen nucleophiles: direct versus allylic substitution

A remarkable regioselectivity difference in the Lewis-acid catalyzed reactions of 2-C-acteoxymethyl glycals with thiophenols and phenols has been observed. The reaction with thiophenols led to preferential formation of a new class of compounds viz. 2-C-arylthiomethyl glycals via direct attack at the C-2 side chain primary carbon bearing the leaving group. In contrast, phenols were reported to afford predominantly 2-C-methylene-O-aryl glycosides via allylic attack at the anomeric carbon. The observed results correlate well with the HSAB principle proposed earlier for similar type of reactions with simple glycals. In addition, formation of an unusual bis-thioarylated product in presence of an excess of thiophenol is also reported.     

Syntheses and structures of anomeric quaternary ammonium β-glucosides and comments on the anomeric C-N bond lengths

We report convenient syntheses of anomeric quaternary ammonium β-glucosides in both protected and deprotected forms, together with X-ray structural investigations of two of the products. Both the quaternisation of a protected anomeric N,N-(dimethylamino)glucose, derived in two high-yielding steps from the anomeric azide, and the direct reaction of glucose or 6-O-trityl glucose with a secondary amine, followed by protection and quaternisation, are viable routes. We also discuss the significance, in terms of stereoelectronic effects, of the observed C-N bond lengths and the stabilities of the products.     

Stereoselective O-glycosylation reactions using glycosyl donors with diphenylphosphinate and propane-1,3-diyl phosphate leaving groups

Glycosyl donors having a diphenylphosphinate and a propane-1,3-diyl phosphate leaving group were easily prepared by the addition of the anomeric hydroxyl group of 2,3,4,6-tetra-O-benzyl-α,β-d-glucopyranose to diphenylphosphinic and propane-1,3-diyldioxyphosphoryl chlorides. These glycosyl donors were selectively glycosylated with a number of primary and secondary oxygen nucleophiles in the presence of trimethylsilyl triflate (TMSOTf). The use of 1,3-diyl phosphate resulted in the stereoselective formation of β-O-linked glycosides.     

Ferrier Reaction: The first synthesis of 2,3-unsaturated seleno-glycosides by using alkyl(aryl) hydroselenides as the nucleophile and Hf(OTf)4 as the catalyst

By using Hf(OTf)₄ as the catalyst, a series of 2,3-unsaturated-Se-glucosides have been synthesized for the first time from tri-O-acetyl-d-glucal, 2,4,6-tri-O-benzyl-d-glucal, 3,4-di-O-acetyl-l-rhamnal and ((2R,3S)-3-acetoxy-2,3-dihydrofuran-2-yl) methyl acetate with PhSeH or alkyl(aryl) hydroselenides as the nucleophile in good yield and high anomeric selectivity.     

Synthesis of 1-O-(Methylthio)thiocarbonyl Sugar Derivatives Bearing Acyl Protective Groups Using Phase Transfer Catalysis Methods

Abstract

2,3,4,6-Tetra-O-acetyl-D-glucopyranose (1) was successfully transformed to an anomeric mixture of 2,3,4,6-tetra-O-acetyl-1-O-(methylthio)thiocarbonyl-D-glucopyranose (2) by liquid - liquid and solid - liquid phase transfer methods. Similar anomeric free sugar derivatives bearing acetyl or benzoyl protective groups were also smoothly converted to the corresponding 1-O-(methylthio)thiocarbonyl derivatives. Thermal rearrangement of 1-O-(methylthio)thiocarbonylfuranose derivatives proceeded well to give 1-S-methylthiocarbonyl-1-thiofuranose derivatives.     

Sm(OTf)3 as a highly efficient catalyst for the synthesis of 2,3-unsaturated O- and S-pyranosides from glycals and the temperature-dependent formation of 4-O-acetyl-6-deoxy-2,3-unsaturated S-pyranosides and 4-O-acetyl-6-deoxy-3-alkylthio glycals

By using Sm(OTf)₃ as the catalyst, synthesis of 2,3-unsaturated-glycosides has been performed. A series of 2,3-unsaturated glycosides were obtained from 3,4,6-tri-O-acetyl–d-glucal or 3,4-di-O-acetyl-l-rhamnal under mild reaction conditions in good yield and high anomeric selectivity. It was found that under certain conditions, reaction of 3,4-di-O-acetyl-l-rhamnal with thiol leads to temperature-dependent formation of C-1-S and C-3-S product. A temperature-dependent profile of the yield of these two products is given.     

Propargyl mediated intramolecular aglycon delivery (IAD): applications to the synthesis of core N-glycan oligosaccharides

The use of propargyl mediated intramolecular aglycon delivery (IAD) for the synthesis of the key Manβ(1→4)GlcNAc linkage of N-glycan oligosaccharides, including the core N-glycan pentasaccharide, is investigated. Isomerisation of a 2-O-progargyl group of manno thioglycoside donors to an allene is followed by iodonium ion mediated mixed acetal formation with the 4-OH of protected GlcNAc acceptors, and subsequent intramolecular glycosylation occurs with complete control of anomeric stereochemistry to form the Manβ(1→4)GlcNAc linkage. A variety of linear and convergent approaches (1+2, 3+1, 3+2) to the core pentasaccharide are investigated as means of probing the generality and limitations of this type of intramolecular aglycon delivery for the formation of β-mannoside linkages in complex oligosaccharides.     

Characterization of positional and anomeric isomers of methyl 2-O- and 3-O-sulfo-D-glucopyranosiduronic acids and methyl 2-O- and 3-O-sulfo-D-glucopyranosides by secondary ion mass spectrometry

Secondary ion mass spectrometry (SIMS) of anomeric pairs of methyl 2-O- and 3-O-sulfo-D -glucopyranosiduronic acids and methyl 2-O- and 3-O-sulfo-D -glucopyranosides show the deprotonated molecule in the negative-ion mode and ammoniated and sodiated molecules in the positive-ion mode. The four isomers were distinguished from each other by linked scanning at constant B/E in negative- and positive-ion SIMS, which gave information characteristic of the position of the sulfate group and even the configuration of the anomeric methoxy group. The main fragmentation processes correspond to the loss of methanol and the elimination of SO₃.     

Modulation of the stereoselectivity and reactivity of glycosylation via (p-Tol)2SO/Tf2O preactivation strategy: From O-, C-sialylation to general O-, N-glycosylation

We make a review on the progress of the (p-Tol)₂SO/Tf₂O preactivation strategy for general glycosylation using thioglycosides or sialyl sulfoxide as donors.     

Synthesis and Antitubercular and Antibacterial Activities of Triethylammonium 2-Acetamido-3,4,6-tri-<Emphasis Type="Italic">O</Emphasis>-acetyl-2-deoxy-D-glucopyranosyl Decyl Phosphate

Phosphorylation of 2-acetamido-3,4,6-tri-O-acetyl-2-deoxy-D-glucose at the anomeric hydroxy group gave previously unknown triethylammonium 2-acetamido-3,4,6-tri-O-acetyl-2-deoxy-D-glucopyranosyl phosphonate, and successive treatment of the latter with decan-1-ol and aqueous iodine afforded triethylammonium 2-acetamido-3,4,6-tri-O-acetyl-2-deoxy-α-D-glucopyranosyl phosphate.     

Fragmentation of carbohydrate anomeric alkoxyl radicals. Synthesis of highly functionalized chiral vinyl sulfones

The reaction of derivatives of 3-acetyl-d-glucal, 3-acetyl-l-rhamnal, 3-acetyl-d-galactal, and 3-acetyl-d-lactal with sodium benzenesulfinate in acid medium catalyzed by HgSO₄ afforded diastereoisomeric mixtures of the corresponding 2,3-dideoxy-3-(phenylsulfonyl)-hexopyranoses through a Ferrier rearrangement. The anomeric alkoxyl radical fragmentation of these γ-hydroxy sulfones using the system (diacetoxyiodo)benzene and iodine gave vinyl sulfones with structures of 1,2-dideoxy-4-O-formyl-2-(phenylsulfonyl)-pent-1-enitol and configurations d-erythro, l-erythro, and d-threo at the two stereogenic centers.     

RuCl3·3H2O as catalyst for Ferrier rearrangement: an efficient procedure for the preparation of pseudoglycosides

By using RuCl₃·3H₂O as catalyst, an improved method for the synthesis of 2,3-unsaturated-glycosides has been established. A series of 2, 3-unsaturated-glucosides were obtained from 2,4,6-tri-O-acetyl-d-glucal or 3,4-di-O-acetyl-6-deoxy-l-glucal in good yield and high anomeric selectivity.     

Synthesis of a useful anomeric thioacetate of an N-acetyllactosamine derivative and its application

A novel anomeric β-thioacetate of an N-acetyllactosamine derivative was efficiently synthesized in high yield from the known 2-azido glycosyl chloride using thioacetic acid as a convenient reagent. The synthesis involved not only an S_N2 replacement of the chloride by a carbothiolate anion but also a reductive acetamidation of the azide group. Applications of the thioacetate for glycosidation were demonstrated to provide both O- and S-glycosides in high yields. Furthermore, both intermediates gave a new class of glycoclusters that included thioglycosidic linkages.     

Alkoxyl radical fragmentation of 3-azido-2,3-dideoxy-2-halo-hexopyranoses: a new entry to chiral polyhydroxylated 2-azido-1-halo-1-alkenes

A new general two-step methodology for the synthesis of chiral fluoro, chloro, bromo and iodo vinyl azides from carbohydrate-derived halohydrins has been developed. The anomeric alkoxyl radical fragmentation of 3-azido-2,3-dideoxy-2-halo-pyranoses under oxidative conditions with (diacetoxyiodo)benzene and iodine gave 2-azido-1,2-dideoxy-1-halo-1-iodo-alditols, which by chemoselective dehydroiodination afforded (Z,E)-2-azido-1,2-dideoxy-1-halo-4-O-formyl-pent-1-enitols in good overall yields. Preliminary thermolysis and photochemical studies of these compounds for the synthesis of hitherto unknown disubstituted 2-halo-3-alkyl-2H-azirines have also been accomplished.     

Regioselective removal of the anomeric O-benzyl from differentially protected carbohydrates

A mild, regioselective deprotection of the anomeric O-benzyl from multi-functionally protected carbohydrates via catalytic transfer hydrogenation is described. The protocol is tolerant of O-benzyl and O-benzylidene protections at non-anomeric positions, groups which are normally labile under typical hydrogenolysis conditions.     

Iron(III) triflate,a new efficient catalyst for Type I Ferrier Rearrangement

By using iron(III) triflate as catalyst, an improved method for the synthesis of 2,3-unsaturated-O-glycosides has been established. A series of 2,3-unsaturated-O-glucosides were obtained from 2,4,6-tri-O-acetyl-d-glucal in good yield and high anomeric selectivity.     

Using density functional theory to calculate the anomeric effect in hydroxylamine and hydrazide derivatives of tetrahydropyran

Little is known about the magnitude of the anomeric effect in N-glycosylated oxyamines and hydrazides, limiting efforts toward the design of chemoselective acceptors that impose a stereochemical preference on glycosylation reactions. Thus, density functional theory (DFT) calculations were conducted to estimate the magnitude of the anomeric effect in N,O-dimethyl-N-(tetrahydro-2H-pyran-2-yl)hydroxylamine (1) and N'-(tetrahydro-2H-pyran-2-yl)acetohydrazide (3). The results show that N,O-dimethyl-N-(tetrahydro-2H-pyran-2-yl)hydroxylamine (1) displays a significant anomeric effect (AE_corr = 1.38 kcal/mol) and that N'-(tetrahydro-2H-pyran-2-yl)acetohydrazide (3) displays a modest anomeric effect (AE_corr = 0.54 kcal/mol).